OXA-48-Like β-Lactamases: Global Epidemiology, Treatment Options, and Development Pipeline

Boyd, Sara E ORCID: 0000-0001-9935-5263, Holmes, Alison ORCID: 0000-0001-5554-5743, Peck, Richard ORCID: 0000-0003-1018-9655, Livermore, David M and Hope, William ORCID: 0000-0001-6187-878X
(2022) OXA-48-Like β-Lactamases: Global Epidemiology, Treatment Options, and Development Pipeline. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 66 (8). e0021622-.

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Modern medicine is threatened by the rising tide of antimicrobial resistance, especially among Gram-negative bacteria, where resistance to β-lactams is most often mediated by β-lactamases. The penicillin and cephalosporin ascendancies were, in their turn, ended by the proliferation of TEM penicillinases and CTX-M extended-spectrum β-lactamases. These class A β-lactamases have long been considered the most important. For carbapenems, however, the threat is increasingly from the insidious rise of a class D carbapenemase, OXA-48, and its close relatives. Over the past 20 years, OXA-48 and "OXA-48-like" enzymes have proliferated to become the most prevalent enterobacterial carbapenemases across much of Europe, Northern Africa, and the Middle East. OXA-48-like enzymes are notoriously difficult to detect because they often cause only low-level <i>in vitro</i> resistance to carbapenems, meaning that the true burden is likely underestimated. Despite this, they are associated with carbapenem treatment failures. A highly conserved incompatibility complex IncL plasmid scaffold often carries <i>bla</i><sub>OXA-48</sub> and may carry other antimicrobial resistance genes, leaving limited treatment options. High conjugation efficiency means that this plasmid is sometimes carried by multiple <i>Enterobacterales</i> in a single patient. Producers evade most β-lactam-β-lactamase inhibitor combinations, though promising agents have recently been licensed, notably ceftazidime-avibactam and cefiderocol. The molecular machinery enabling global spread, current treatment options, and the development pipeline of potential new therapies for <i>Enterobacterales</i> that produce OXA-48-like β-lactamases form the focus of this review.

Item Type: Article
Uncontrolled Keywords: OXA-48 beta-lactamase, treatment, pharmacology, drug development, OXA-48, beta-lactamases, epidemiology
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User: Symplectic Admin
Date Deposited: 28 Oct 2022 14:51
Last Modified: 05 Oct 2023 21:54
DOI: 10.1128/aac.00216-22
Open Access URL: https://spiral.imperial.ac.uk/handle/10044/1/98647
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3165845